Attempts were made to initiate hormone-dependent tumor (HDT) transformation in ductal phase mammary outgrowths. These outgrowths, when carried in virgin GR/A mice, were not tumorous and usually resembled the host's mammary glands. After 2-3 months' initial growth, the following hormone treatments were initiated: 1) An isologous pituitary was implanted into each fat pad having previously received an HDT transplant. Some neoplastic transformation of the pregnancy-dependent tumor outgrowth occurred after 1-2 months; all 10 mammary glands were well stimulated and had many hyperplastic alveolar nodules. 2) In experiments involving exogenous hormone administration, estrogen or progesterone administered alone caused no neoplastic changes in the 2- to 3-month-old ductal phase outgrowths. However, 1 mg progesterone plus 1 mug estrogen daily given sc for 3 weeks to both ovariectomized and intact mice with HDT transplants caused neoplastic changes in the outgrowths and induced small ductal hyperplasias in the host glands. Termination of hormone treatment resulted in a return to the normal ductal structure. The addition of 100 mug prolactin and 100 mug growth hormone to the progesterone and estrogen mixture did not further alter transplants but increased stimulation to the host glands.